We are continuing to study the immunopathogenesis of human digestive tract and other cancers by focusing on biological markers produced by benign and malignant mucous membranes. We are improving the clinical use of biological markers, CEA and others, in the management of patients. Our studies emphasize the key role of the liver in regulating CEA and other circulating marker glycoproteins. We will study the mechanism by which CEA and other glycoproteins are cleared from the blood, bound to the hepatic cell and Kupffer cell and excreted, as well as its clinical implications. We will systematically study glycoprotein markers (CEA, ZGM and alpha-1-acid glyco-protein) in benign, malignant and transitional mucosa by combining immunoperoxidase staining, "mucus" stains including sialo-and sulfomucins, correlating these with tissue differentiation, thus providing the basis for an improved glycoprotein characterization of tumors. We will assess the usefulness of these tumor markers in pathological diagnosis, including distinguishing between undifferentiated and well differentiated tumors and undifferentiated adenocarcinoma and lymphoma. We propose a new method for quantitating tumor glycoproteins in histological sections of human tumor tissues using quantitative immunoelectrophoretic analysis. Using a combined immunochemical and immunohistological approach and xenogeneic and monclonal antibodies, we will search for new markers of digestive tract epithelial mucosa looking for markers which reflect differing cell types and varying differentiation.